Intermolecular Enantioselective Benzylic C(sp3)-H Amination via Cationic Copper Catalysis

06 February 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3)H functionalization by a hydrogen-atom transfer (HAT) process has emerged as a straightforward and powerful tool for the synthesis of chiral amines, while intermolecular enantioselective C(sp3)H amination remains elusive. In this article, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3)H amination with peroxide as oxidant. This mild yet straightforward method transforms an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities. The protocol has good functional group tolerance and broad substrate scope. More importantly, the method can be applied to synthesizing bioactive molecules and chiral drugs. Preliminary mechanistic studies indicate that benzylic radicals resulting from the HAT process are involved in the amination reaction.


C-H Amination
Copper catalysis
Chiral amine

Supplementary materials

Supporting Information for Intermolecular Enantioselective Benzylic C(sp3)-H Amination via Cationic Copper Catalysis
Supporting Information


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